11-113449697-T-C

Variant names:

• chr11-113449697-T-C
• rs4245148
• NM_000795.4:c.-31-25015A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.-31-25015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,858 control chromosomes in the GnomAD database, including 48,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (48944 hom., cov: 30)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 17 publications found

Genes affected

DRD2 (HGNC:3023): (dopamine receptor D2) This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-25015A>G		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-25015A>G		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3
DRD2	ENST00000346454.7	c.-31-25015A>G		intron_variant	Intron 1 of 6	1		ENSP00000278597.5
DRD2	ENST00000540600.5	n.35-25015A>G		intron_variant	Intron 1 of 5	1
DRD2	ENST00000542616.1	c.-32+24533A>G		intron_variant	Intron 2 of 2	4		ENSP00000441474.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118572 AN: 151740 Hom.: 48927 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118638 AN: 151858 Hom.: 48944 Cov.: 30 AF XY: 0.788 AC XY: 58511 AN XY: 74220

African (AFR) AF: 0.488 AC: 20176 AN: 41314

American (AMR) AF: 0.852 AC: 13006 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3246 AN: 3468

East Asian (EAS) AF: 0.847 AC: 4362 AN: 5152

South Asian (SAS) AF: 0.888 AC: 4234 AN: 4768

European-Finnish (FIN) AF: 0.941 AC: 9976 AN: 10600

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60854 AN: 67982

Other (OTH) AF: 0.828 AC: 1747 AN: 2110

Alfa AF: 0.848 Hom.: 109014

Bravo AF: 0.762

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.34
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4245148; hg19: chr11-113320419;